We have been studying in cats the functional organization of trigeminal brain stem neurones activated in particular by noxious facial an tooth pulp stimuli, and the modulation of this activity by sensory impulses initiated by other orofacial stimuli (e.g., tactile) and by endogenous descending influences. We have found that many cells in nucleus caudalis, considered to be the most essential orofacial pain relay site in the brain stem, show various patterns of discharges evoked by stimulation of orofacial nociceptive afferents; some relay their information directly to thalamus. However, this relay can be suppressed by other orofacial stimuli and particularly by stimulation of periaqueductal gray and nucleus raphe magnus. These sites have recently been implicated in endogenous analgesic mechanisms partly related to the action of narcotics, acupuncture, etc., through the release of endogenous chemicals (e.g., enkephalin). We intend to study these mechanisms further; iontophoretic methods may be particularly worthwhile since we have already found in preliminary published studies that, in contrast to our observed excitatory action of substance P on nociceptive neurones, enkephalin and pain control drugs can suppress such neurones. We have preliminary published evidence that presynaptic regulatory mechanisms contribute to the observed suppressive influences on orofacial nociceptive transmission, and we intend to study these mechanisms further.